Studies of farmers from Midwestern states have suggested risk for several cancers in association with agricultural chemicals such as pesticides. However, the potential exposed population may be much broader, including spouses and children of farmers, and specific minority groups; the health consequences may also encompass a wider spectrum of outcomes than has previously been appreciated. Experimental studies and human studies of acute or high-dose exposures suggest that neurologic, reproductive, renal, and other effects may occur as a result of chronic exposure to pesticides. We are examining a variety of health endpoints in a cohort of 75,000 licensed pesticide applicators and spouses from North Carolina and Iowa. While 80% of eligible applicators have enrolled in the study, response rates for take-home questionnaires are much lower. In order to increase response rates and reduce bias, we have selected three age and sex-specific random samples of enrolled applicators for telephone interviews to complete subsets of the take-home questionnaire when these were not returned by mail. The first of these sub-studies has been completed and response rates were increased from 40% to 85%. Data from these sub-cohorts will be used to examine risk of spontaneous abortion and other reproductive factors; neurologic symptoms; and age at menopause. Using full cohort data from the first two enrollment years, we are exploring the relationship between agricultural exposures and the prevalence of neurologic symptoms, degenerative eye diseases, menstrual and reproductive dysfunction, and several chronic diseases. Preliminary results are consistent with animal data in suggesting that macular degeneration and other causes of visual impairment may be associated with specific farm practices. We are also exploring sociodemographic and farming practice differences between African American and other farmers and exposure patterns of spouses and children who are not themselves pesticide applicators. A subcohort of 1000 African American farmers was successfully enrolled through churches in NC.